Dynamic aspects of cancer cell populations in metastasis

Consideration of the entire metastatic process reveals it to be very inefficient in terms of cancer cells. Of the millions of cells released from primary cancers, relatively few metastases result. This disparity implies that in some way the process is selective. Some evidence will be reviewed that indicates that cancer cells in metastases are in some way different from those in the primary cancer from which they arose. Primary cancers and their metastases, then, should possibly be regarded as distinct entities when one is considering therapy or seeking an understanding of the fundamental aspects of metastasis. In this presentation some nonexclusive mechanisms will be discussed that could be responsible for differences between primary and secondary cancers. These include: 1) Random (statistical) selection of metastasis-forming cells; 2) The existence of genotypic metastatic subpopulations; 3) The existence of transient metastatic "compartments" within primary cancer; 4) Site-induced changes (modulation) occurring in the metastasizing cells after they arrive in the target organ; 5) A combination of the above.